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Neural mechanisms of action learning in mouse models

Final Report Summary - NEUROACTION (Neural mechanisms of action learning in mouse models)

Executive Summary:

The process of perfecting an action through repetition leads to more accurate, precise and faster performance. The neural circuits involved in the consolidation of these different aspects of skill learning remain somewhat unknown. Using mice expressing fluorescent proteins in direct and indirect striatal circuits, we found that extended training is accompanied by subregion-specific circuit plasticity in the dorsal striatum, with glutamatergic input to the indirect pathway being more potentiated late in learning. However, during the process of doing the experiments of the grant we realized that while the rotarod allows for the reliable study of skill consolidation, it does not permit easily the dissection of the different aspects of motor learning described above. We therefore developed a self-paced operant task in which mice have to press a lever at increasingly faster speeds to obtain food reward. We used several versions of this task in combination with circuit-specific optogenetic manipulations to investigate which pathways are involved in initiating a well-learned skill or performing it. We found that inhibiting or stimulating either the direct and indirect pathway before affects the initiation of the action sequence. However, after sequence initiation we found that inhibiting or stimulating the direct and indirect pathways of striatum had dichotomous effects. Finally, we have also developed a method to record from identifiable of cell types in vivo, and find that different neurons from the direct and indirect pathway are differentially involved at different phases of skill execution (initiation or performance). These findings have important implications for understanding the learning and execution of skilled movements, and the impairments observed in basal ganglia disorders like Parkinson’s and Huntington’s disease.